FDA Approves Atezolizumab for Advanced Urothelial Carcinoma

The U.S. Food and Drug Administration (FDA) today granted accelerated approval to atezolizumab (Tecentriq) for the treatment of urothelial carcinoma, the most common type of bladder cancer. This is the first programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) inhibitor to be approved to treat this type of cancer.

Atezolizumab is approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or following platinum-containing chemotherapy or within 12 months of receiving neoadjuvant or adjuvant platinum-containing chemotherapy.

“[Atezolizumab] provides these patients with a new therapy targeting the PD-L1 pathway,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Products that block PD-1/PD-L1 interactions are part of an evolving story about the relationship between the body’s immune system and its interaction with cancer cells.”

Atezolizumab targets the PD-1/PD-L1 pathway. By blocking these interactions, the drug may help the body’s immune system fight cancer cells. Atezolizumab is the first FDA-approved PD-L1 inhibitor and the latest in the broader class of PD-1/PD-L1 targeted biologics approved by the FDA in the past 2 years.

Safety and Efficacy

The safety and efficacy of atezolizumab were studied in the IMvigor 210 study, a single-arm clinical trial involving 310 patients with locally advanced or metastatic urothelial carcinoma. The primary endpoint of the trial was objective response rate—the percentage of patients who experienced complete or partial shrinkage of their tumors. The study also looked at the difference in effect based on “positive” vs“negative” expression of the PD-L1 protein on patients’ tumor-infiltrating immune cells.

Among all patients, 14.8% of participants experienced at least a partial shrinkage of their tumors, an effect that lasted from more than 2.1 to more than 13.8 months at the time of the response analysis. In patients with PD-L1–positive tumor-infiltrating immune cells, 26% of participants experienced a tumor response, compared to 9.5% of participants who were PD-L1–negative.

Although patients who received atezolizumab experienced a tumor response across the study, the greater effect in those who were classified as being PD-L1–positive suggests that the level of PD-L1 expression in tumor-infiltrating immune cells may help identify patients who are more likely to respond to treatment with atezolizumab. Therefore, the FDA has also approved the Ventana PD-L1 (SP142) assay to detect PD-L1 protein expression levels on patients’ tumor-infiltrating immune cells and help physicians determine which patients may benefit most from treatment with atezolizumab.

The most common side effects of treatment with atezolizumab were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. Atezolizumab also has the potential to cause infection and severe immune-mediated side effects involving the lung, colon, and endocrine system.